Environmental exposure to the human carcinogen, benzene, is an important public health concern because of its prevalence, particularly in cities. Further research is needed to identify and protect groups and individuals at increased risk for adverse health effects from benzene exposure. The incorporation of biomarkers would substantially strengthen such research by providing information on individual variation in absorption and metabolism. This variation is an essential factor in the markedly different human susceptibility for toxic outcomes at similar exposure levels. This group recently completed a pilot study which used biomarkers to explore environmental benzene exposure in an urban area. They measured trans, trans-muconic acid (ttMA), an aliphatic metabolite of benzene, and cotinine [to assess the benzene source - environmental tobacco smoke (ETS)], in the urine of 79 children who were already overexposed to one urban toxicant, lead. They measured ttMA in more than 70% of these children and found several unexpectedly high values. Cotinine levels were also strikingly elevated with 79.5% over 30 ng/mg creatinine, a level commonly associated with household exposure. These results suggest that they have identified a group at high risk for environmental benzene exposure. Two studies are proposed for further investigation of these findings. The first will determine whether the benzene biomarkers used adequately measure internal dose in environmental exposure. This will be accomplished by comparing the established exposure measurement, personal air benzene, with two biomarkers, ttMA and S-phenylmercapturic acid (S-PMA), in pre-school inner-city children and their mothers. These data will also be used to determine if age-related or ethnic differences in benzene metabolism exist. A second study, in a subset of mother-child pairs from the initial investigation, will include the above measures, along with the addition of breath benzene and more frequent biomarker assessments over the study day. Such data will be useful for comparison with animal and in vitro work to facilitate extrapolation in risk assessment. These studies provide the basis for a research agenda aimed at identifying and improving protection of susceptible groups exposed to environmental toxicants.